A newly developed prognostic metabolite score (PMS) was found to be useful in distinguishing heart failure (HF) with midrange (HFmrEF) vs preserved (HFpEF) or reduced ejection fraction (HFrEF), according to the results of a quantitative metabolomics study published in the Canadian Journal of Cardiology.

Patients with HF (n=446) and control individuals (n=182) were recruited at the First Affiliated Hospital of Jinzhou Medical University in China between 2015 and 2018. HFmrEF was defined as a left ventricle ejection fraction (LVEF) between 40% and 49%, HFpEF as LVEF ≥50%, and HFrEF as LVEF <40%. All participants were assessed for routine HF biochemical indices and 102 metabolites were quantified using a targeted approach.

Among the participants with HF, 39.4% had HFpEF, 33.9% had HFrEF, and 26.7% had HFmrEF. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, red blood cell distribution width, lactate dehydrogenase, alanine transaminase, aspartate transaminase, total bilirubin, direct bilirubin, and creatinine were all found to increase with the severity of HF (P <.05).

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The metabolic profile of patients with HFrEF had the highest deviation (significant differences for 36 metabolites) compared with that of control participants (P <.05). Patients with HFpEF and HFmrEF had significant differences compared with control individuals for 35 and 32 metabolites, respectively. A total of 15 metabolites were shared between participants with HF (of any severity) and control individuals.

For patients with available follow-up data (80.3%), there were 156 rehospitalizations or HF-related deaths within 1.5 year. Based on data from these patients, the investigators developed a PMS using a lasso-penalized regression analysis and including 9 metabolites. Patients with a higher PMS (>1.012) had lower survival rates (P <.001). Similarly, patients with higher natural logarithm NT-proBNP, Ln(NT-proBNP) (>8.67) had lower survival rates (P <.001).

The PMS had a better prognostic utility compared with Ln(NT-proBNP) (hazard ratio [HR], 1.62; 95% CI, 1.25-2.1 vs HR, 1.23; 95% CI, 0.94-1.61; P <.001). In addition, the PMS had a greater ability to differentiate between HF subtypes than Ln(NT-proBNP): HFpEF (HR, 1.421; P =.037 vs HR, 1.32; P =.061, respectively); HFmrEF (HR, 1.587; P <.001 vs 1.309; P =.027, respectively)), and HFrEF (HR, 1.614; P =.001 vs HR, 1.152; P =.382, respectively)).

A potential limitation of this study was that a full metabolite spectrum was not collected, so that other metabolites may improve the diagnostic quality of PMS.

“Compared with conventional clinical risk factors, including BNP measurements, the PMS generated from the 9 metabolite features improved prognostic values for patients with HFmrEF and HFrEF,” concluded the study authors.


Zhao H, Shui B, Zhao Q, et al. Quantitative metabolomics reveals heart failure with midrange ejection fraction as a distinct phenotype of heart failure. Can J Cardiol. 2020;S0828-282X(20)30297-X. doi:10.1016/j.cjca.2020.03.024

This article originally appeared on The Cardiology Advisor